Prostate Cancer Xenograft

Altogen Labs validated Prostate Cancer Xenograft animal models:

DU-145,  LNCaP,  PC-3

Xenotransplantation studies have been a backbone of oncology research for four decades, and provide an effective research and evaluation environment for novel pharmaceutical compounds. Typically, these studies involve the implantation of tumorigenic human cell lines into immunocompromised mice, providing scientists with an in vivo model of tumor behavior in which to perform experiments including screening of novel cancer therapies, studies of cell behavior, and examination of metastasis. Patient-derived xenografts are a fundamental part of in vivo pharmacological research, aiding in the translation from benchtop to bedside.

Prostate cancer are generally slow growing and sometimes have no symptoms in early stages. Some symptoms include bloody urine (hematuria), difficulty urinating, painful urination (dysuria), back pain or pelvis pain. Risk factors include old age, race and family history. Mutated genes implicated in contributing to the development of prostate cancer include BRCA1, BRCA2, HPC1, TMPRSS2-ETS, TMPRSS2-ERG, TMPRSS2-ETC1/4 and the vitamin D receptor. Cellular pathways associated with the pathophysiology of prostate cancer include PTEN, PI3k/Akt, pacrophage inhibitory cytokine-1 (MIC-1) and FAK. Most prostate cancers occur in epithelial cells and so are classified as adenocarcinomas. In this case, cancer cells are relatively confined and referred to as prostatic intraepithelial neoplasia (PIN). After these cells progress they can invade the stroma and nearby organs. Diagnostic methods include medical imaging  (MRI, higher resolution, or ultrasound, lower resolution) and tissue biopsies. Tumor markers include elevated levels of prostate-specific antigen and Ki-67. Treatment includes surveillance, brachytherapy, external beam radiation therapy, cryosurgery, HIFU, hormonal therapy, cryotherapy and the cancer vaccine Sipuleucel-T. It is the nature of the prostate to be hormone sensitive and dependent, and many hormone dependent prostate cancers become treatment resistant within three years; such cases have been referred to as “hormone-refractory prostate cancer” and “androgen-independent prostate cancer” and are generally castration-resistant. Combination chemotherapy and immunotherapy are often used in these cases to increase survival by months and research has been looking into stem-like directed differentiation therapy. Early stage detection typically has a 5-year survival rate while with late stage detection this drops to 29%.

Using human xenograft models of prostate cancer, as previously mentioned, is a powerful research tool, and there are several models of prostate cancer to choose from. There are links above to some of the most common tissue culture models that Altogen Labs has available, summarized in the table below. Models are often selected based on morphology, genetics, histology, early vs. late stage phenotype, invasive/aggressive properties, and abnormal protein expressions (usually relating to cell cycle, apoptosis, growth and angiogenesis). The goal of xenografts and murine models is to mirror human pathology and disease as closely as possible so that accurate insights into cellular events are achieved. This aspect is particularly critical with preclinical drug testing for accurately evaluating compound efficacy.

Cell LineCharacteristics
DU-145·    Epithelial human prostate carcinoma from metastatic parieto-occipital brain site

·    Hormone insensitive

·    Prostate-specific antigen negative

·    Androgen-receptor positive

·    Hypotriploid karyotype

·    Morphology includes microvilli, desmosomes, tonofilaments, heterogeneous lysomes, mitochondria and well developed Golgi

LNCaP·    Epithelial prostate carcinoma derived from a human supraclavicular lymph node metastasis

·    Hypotetraploid karyotype

·    Androgen and estrogen receptor positive

·    Expresses human prostatic acid phosphatase and prostate specific antigen

·    Responsive to 5-α-dihydrotestosterone

PC-3·    Isolated from a bone marrow metastasis of human grade IV epithelial prostate cancer

·    Established after patient went through androgen suppression therapy

·    Exhibits high metastatic potential

·    Expresses HLA A1 and A9

·    Prostate specific antigen negative

·    Exhibits similar characteristics to small cell neoendocrine carcinoma

Altogen Labs is one of the leading biology contract research organization (CRO) based in Austin, Texas. Altogen Labs provides years of expert research in xenograft experiments taking advantage of the comprehensive expertise the company has developed in the use of human tumor xenografts for research and clinical purposes. Altogen Labs offers a complete suite of laboratory services, including:

  • xenotransplantation study design
  • selection of appropriate cancer model/cell line
  • host animal selection
  • subcutaneous or orthotopic xenografting
  • daily observation of experimental subjects
  • post-experiment analysis, including serum collection and histology

Mouse strains available at Altogen Labs:

Mouse typeT cellsB cellsNK cellsCoatOther Notes
CD1NoYesYesWhite/albinoOutbred
B6YesYesYesWhite/albinoInbred
Balb/cNoYesYesNude, albinoInbred
Balb/SCIDNoNoYesWhiteInbred
NOD/SCIDNoNoImpairedWhiteInbred
Nu/nuNoYesYesNudeOutbred
CD57BLYesYesYesDark brown/blackInbred
CB17YesYesYesWhiteInbred
NSGNoNoNoWhiteInbred
Swiss NudeNoYesYesNudeOutbred

 

About the models

CD1

This model originates from a non-inbred Swiss stock of the 1920s from the Centre Anticancerux Romand (Lausanne, Switzerland). Outbred stocks are generally used for their genetic variability.

B6

This strain of mouse arose from a spontaneous mutation in the C57BL/6 strain resulting in a coisogenic albino mutant. These mice have a mutant tyrosinase gene.

Balb/c

This strain of nude mouse was developed in the 1980s through many crosses and backcrosses and remains to be an inbred model. Balb/c mice do not have a thymus and therefore cannot produce T-cells and are considered immunodeficient. Balb/c mice are often used for their easy breeding and similar weights (low-variation) of males and females. They are also used for monoclonal antibody production.

Balb/SCID

This mouse model lacks functioning T and B cells but do have functioning NK cells which limits engraftment. These mice are sensitive to irradiation and have functioning macrophages, dendritic cells and complement activity. Some cancer cell lines show improved engraftment over nude models in Balb/SCID mice.

NOD/SCID

The homozygous SCID mutation results in impaired T cell and B cell lymphocyte development. The NOD characteristic results in impaired natural killer cell function. NOD/SCID mice also lack macrophage and dendritic cell activity as well as reduced complement activity. These mice have a non-obese diabetic and insulitis background and low cytokine production. NOD/SCID mice exhibit a 36-week median survival due to the development of thymic lymphomas, which limits their use to short-term experiments.

Nu/nu

These mice originate from the National Institute of Health (NIH). Originally thought to be BALB/C congenic mice, once it was discovered that these mice were outbred they were determined to be of their own strain. These mice do not have a thymus, or T-cells, and are nude immunodeficient models.

CD57BL/6

This laboratory mouse strain was the 2nd mammalian species to ever have its genome published in entirety. They originate from the Bussey Institute for Research in Applied Biology in 1921. These mice are often selected for easy breeding and availability of congenic strains. These mice are particularly sensitive to odors, noise, pain, cold, alcohol and morphine addiction.

CB17

CB17 mice are of a congenic strain that carry the immunoglobulin heavy chain allele (Igh-1b) from a C57BL/Ka on a BALB/c background. They are an ideal control for the CB17/SCID immunodeficient mouse model

NSG

Also known as NOD scid gamma, these mice are deficient in NK, T and B cells as well as multiple cytokine pathways. They also have reduced dendritic cell function and defective macrophage activity and lack a complement system. They are one of the most immunodeficient models available and unlike NOD/SCID mice, NSG mice do not develop thymic lymphomas and can be used for long-term experiments.

Swiss Nude

These mice originate from the 1974 Gustave Roussy Institute (Villejuif, France) Swiss stock. They are T cell deficient, nude and albino.

All laboratory studies are performed by experienced personnel in a GLP-compliant and IACUC-regulated facility in Austin, Texas. Please contact us at info@altogenlabs.com, or call 512-433-6177 to discuss xenograft study details.